Biomedical subjects

J Cano

Publications and source records attributed to J Cano.

At least 109 records · Page 6Linked to original sources

PubMed1995

Complex I inhibitor effect on the nigral and striatal release of dopamine in the presence and absence of nomifensine.

The effect of inhibitors of complex I respiratory chain--1-methyl-4-phenylpyridinium ion (MPP+, 10 microM) and rotenone (100 microM)--on the release and metabolism of dopamine was studied by in vivo microdialysis in the striatum and substantia nigra. Both compounds produced a marked increase in the release of dopamine in the striatum and substantia nigra, which was diminished when nomifensine (20 microM) was included in the perfusion fluid. The 3,4-dihydroxyphenylacetic acid (DOPAC) extracellular output was decreased under MPP+ (10 microM) perfusion in the striatum and substantia nigra, in the presence and in the absence of nomifensine (20 microM). However, perfusion of rotenone (100 microM) increased or had no effect on DOPAC outflow. Homovanillic acid levels were affected in the same way as DOPAC levels, but the changes were always much less pronounced. These results suggest that the neurotoxic action of MPP+ or rotenone is similar in the striatum and substantia nigra, indicating the importance of the dopamine uptake system in this neurotoxic action of MPP+ or rotenone, also suggesting that the dopamine uptake system could have low selectivity and also transports other substances such as rotenone.

1-Methyl-4-phenylpyridinium↗

PubMed1995

Intrastriatal quinolinic acid injections protect against 6-hydroxydopamine-induced lesions of the dopaminergic nigrostriatal system.

We tested the effect of intrastriatal quinolinic acid (QA) injections 2 weeks before subsequent intrastriatal injections of 6-hydroxydopamine (6-OHDA). Levels of DA and its metabolites were measured 2 days and 21 days after lesioning the dopaminergic nigrostriatal system with 6-OHDA. Intrastriatal 6-OHDA injections in the absence of prior treatment of QA significantly decreased dopamine (DA) and its metabolite levels in striatum but not in substantia nigra at day 2, and in striatum and substantia nigra at day 21, a clear indication of a time-dependent retrograde axonal degeneration of substantia nigra cell bodies. Intrastriatal QA injections 2 weeks before subsequent intrastriatal injection of 6-OHDA partially prevented the 6-OHDA-depleting effect on DA and its metabolite levels in both striatum and substantia nigra 21 days after 6-OHDA injection. However, no statistically significant differences were found between QA + 6-OHDA- and 6-OHDA-treated animals at day 2. Our results suggest that intrastriatal QA injections partially prevent the naturally-occurring retrograde axonal degeneration of substantia nigra cell bodies caused by 6-OHDA, and illustrate a target-derived interaction between dopaminergic nerve endings and cell bodies. We suggest that the protective effect found in the QA-injected animals against the neurotoxic action of 6-OHDA is mediated by neurotrophic agents released by activated astroglia.

Animals↗

PubMed1995

The effect of age on the monoamines of the hypothalamus.

Measurement of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) homovanillic acid (HVA), 3-methoxytyramine (3-MT), noradrenaline (NA), 3-methoxy-4-hydroxyphenyl glycol (MHPG) and serotonin (5-HT) and its main metabolite, 5-hydroxyindol-3-acetic acid (5-HIAA) was assessed in hypothalamus and median eminence of aged rats. Age-related changes were not observed in the concentration of NA and its metabolites in median eminence. In contrast, there was a significant NA decrease in aged hypothalamus compared with 12 months (no differences were found compared with 3 months). No significant differences were found in DA concentration and its metabolites in hypothalamus but DA decreased significantly in aged median eminence compared with 12 months. The ratio 5-HIAA/5-HT, indicative of 5-HT turnover, appeared to increase in the hypothalamus and median eminence of the aged rat. Morphological dissimilarities between hypothalamus of young and aged rats were demonstrated using serotonin-immunocytochemistry. A degeneration of the serotoninergic system, denoted by the appearance of enlarged or swollen varicosities, was observed in the hypothalamus of the aged rat. These aberrant serotoninergic fibers may reflect the local degeneration of serotoninergic hypothalamic afferents during ageing. Such differential age-dependent alterations of the serotoninergic system might be responsible for at least some of the functional deficits in aged animals.

Aging↗

PubMed1995

Increase in dopamine turnover and tyrosine hydroxylase enzyme in hippocampus of rats fed on low selenium diet.

We have studied the turnover of dopamine, noradrenaline, and serotonin and their metabolites in hippocampus of adult female rats that were fed control or selenium-deficient diets during 15 days. Under these circumstances, there was an increase of dopamine turnover (4-fold) in rats fed with selenium-deficient diet with respect to controls and also an increase in the tyrosine hydroxylase activity (75.8%), which was the result of the increase of the amount of the enzyme (2-fold), without significant change in the phosphorylation of the tyrosine hydroxylase. In addition the glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase activities have been studied. After selenium-deficient diet, the enzymatic activities of superoxide dismutase and catalase did not show change with respect to the controls; however glutathione reductase and glutathione peroxidase significantly decreased 15% and 29%, respectively. It is concluded that the increase in dopamine turnover seems to be associated with the induction of tyrosine hydroxylase enzyme. In these conditions the decrease in antioxidant capacity may produce a cascade of events, which accelerates the degenerative process, since the increase in dopamine turnover produces an increase in oxygen radical by monoamine oxidase activity.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

5-HT3 receptor agonist induced carrier-mediated release of dopamine in rat striatum in vivo.

1. In vivo microdialysis was used to study the effect of phenylbiguanide (PBG), a 5-hydroxytryptamine3 receptor agonist, on the extracellular output of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the corpus striatum. 2. PBG produced a dose-related (10-500 microM) increase in the release of dopamine (280-2000%). DOPAC and HVA output decreased with the perfusion of PBG. This decrease was similar with 50-500 microM PBG. 5-HIAA output was not affected by any PBG concentration used. 3. When nomifensine (5 microM) was included in the Ringer solution, the effect of PBG on the release of dopamine was ameliorated or inhibited. However, the effect of PBG (50-500 microM) on the extracellular output of DOPAC and HVA was similar in the absence and in the presence of nomifensine (5 microM). 4. Perfusion of MDL 72222, a 5-hydroxytryptamine3 receptor antagonist, at doses of 50 and 100 microM produced similar decreases (50% of controls) and increases (120% of controls) in the extracellular output of dopamine and DOPAC, respectively. HVA and 5-HIAA output levels were not affected by either concentration of MDL 72222. MDL 72222 (10 microM) produced a slight and transient increase in the release of dopamine and a decrease in the extracellular output of DOPAC. HVA and 5-HIAA extracellular output was not affected by MDL 72222 (10 microM) perfusion. 5. Co-perfusion of MDL 72222 (10 and 100 microM) or tetrodotoxin (1 microM) with PBG (50 microM) did not modify the effect produced by PBG (50 microM) alone on the release of dopamine. 6 These results suggest that the effect of PBG on the release of dopamine is mainly carrier-mediated.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Analysis of ceftriaxone and ceftazidime distribution in cerebrospinal fluid of and cerebral extracellular space in awake rats by in vivo microdialysis.

In vivo microdialysis was used to estimate the extracellular concentrations of ceftazidime and ceftriaxone, two expanded-spectrum cephalosporins commonly used in the treatment of bacterial meningitis, in two brain regions (the right corpus striatum and the left lateral ventricle_ of awake, freely moving rats. Antibiotics were administered by constant intravenous infusion at 18 mg/h until steady-state levels were reached. Ceftriaxone levels measured at the steady state in the extracellular space of the corpus striatum (0.80 +/- 0.17 micrograms/ml) were statistically equivalent to those obtained in the cerebrospinal fluid of the lateral ventricle (0.71 +/- 0.15 micrograms/ml). The ratios of these levels in the brain to the steady-state levels in plasma were 0.5 +/- 0.1% for both regions. The postinfusion concentrations of ceftriaxone in the brain declined monoexponentially, with an elimination half-life similar to that obtained in plasma. However, the mean antibiotic concentration of ceftazidime in the striatum (2.2 +/- 0.4 micrograms/ml) was lower (P < 0.001) than that in the lateral ventricle (3.8 +/- 0.5% and 4.0 +/- 1.8%, respectively) were higher than those obtained with ceftriaxone. Moreover, the half-life of ceftazidime elimination from plasma was lower than that obtained in the two brain regions. It was concluded that the in vivo microdialysis technique yields useful data on antibiotic distribution in the extracellular space of the brain, that the distribution may not be homogeneous, and that the decay of postinfusion concentrations in the brain may be different from the decay of postinfusion concentrations in plasma.

Animals↗

PubMed1995

Effect of intraventricular injection of 1-methyl-4-phenylpyridinium: protection by acetyl-L-carnitine.

1-methyl-4-phenylpyridinium (MPP+) is the bioactivated product of 1-methyl-4-phenyl- 1, 2, 3, 6-tetrahydropyridine (MPTP). The neurotoxic action of MPP+ injected intracerebroventricularly (ICV) in the rat has been studied, using dopaminergic systems in the substantia nigra, striatum, olfactory bulb, median eminence and hypophysis. The following results were obtained: (1) Rats with ICV administration of 1 microliter MPP+ solution (62.5 micrograms of MPP+ rat) showed 50% mortality; (2) The ICV administration of MPP+ produced a decrease in dopamine (DA) concentration in different areas of rat CNS studied: striatum (83%), hypophysis (95%) and median eminence (70%). However, olfactory bulb and substantia nigra were not affected; (3) MPP+ by ICV administration produced neurotoxic effect on the dopaminergic system. We also studied the possible protective action of acetyl-L-carnitine (ALC) against the neurotoxic action of MPP+. Rats were intraperitoneally injected daily for 8 days with 100 mg kg-1 of ALC and 3 days from the beginning of the MPP+ treatment; (4) We found that the ALC treatment significantly protected against mortality produced by the ICV injection of MPP+. Rats treated with ALC showed no mortality; (5) We did not find a protective effect on the dopaminergic system studying either catecholamine concentration or measuring tyrosine hydroxylase, neurofilament or glial fibrillary acid protein; (6) The results suggest that the ALC protective action could be related to energy metabolism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1995

Comparative analysis of the rates of chromosome damage induced by bleomycin radiomimetic in human trisomic and diploid lymphocytes: in vitro cultures from a mosaic of a Down's syndrome individual.

Lymphocytes with different chromosome numbers (46,XX and 47,XX + 21) in cultures, were obtained from the blood of a mosaic of a Down's syndrome patient. Their distinctive susceptibility to chromosome damage induced by bleomycin radiomimetic was tested and compared with lymphocytes from healthy individuals. The test showed that the presence of an extra chromosome 21 occurred in parallel with the rise of an intrinsic basal rate of chromosome damage in trisomic cells.

Antimetabolites, Antineoplastic↗

PubMed1994

1-Methyl-4-phenylpyridinium has greater neurotoxic effect after selenium deficiency than after vitamin E deficiency in rat striatum.

The present study was designed to assess the extent of the protective effect of antioxidative capacity of dopaminergic neurons against the possible oxidative stress produced by 1-methyl-4-phenylpyridinium. We have studied the direct effect of 1-methyl-4-phenylpyridinium on striatum slices from rats fed with selenium-deficient or vitamin E-deficient diets for 30 days. Glutathione peroxidase activity decreased significantly after selenium dietary restriction. Our results showed that the effect of 1-methyl-4-phenylpyridinium on dopamine and its metabolites 3,4-dihydroxyphenylacetic acid, homovanillic homovanillic acid and 3-methoxytyramine in animals with both restriction diets was higher than in controls. However, this effect was significantly greater in animals with low selenium diets than with vitamin E-deficient diets in terms of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid, which were all significantly more depleted by 1-methyl-4-phenylpyridinium in selenium-deficient rats than in vitamin E-deficient rats. Therefore, considering changes in the levels of dopamine and its metabolites as an index of 1-methyl-4-phenylpyridinium toxicity, our results seem to indicate that the glutathione-glutathione peroxidase system has a greater protector effect than vitamin E.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Reduction of 1-methyl 1,2,3,4-tetrahydroisoquinoline level in substantia nigra of the aged rat.

The compounds 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ) are endogenous in humans and rats. Whereas TIQ seems to have neurotoxicity, 1-MeTIQ has been described as having a protective effect. In this paper, we report the concentration of TIQ and 1-MeTIQ in two areas especially influenced by aging and Parkinson's disease, the substantia nigra (SN) and striatum (ST), of the rat at different ages. 1-MeTIQ and TIQ were detected in both structures using gas chromatography-mass spectrometry with the higher content of both being in the SN. During the aging process there is a significant decrease (50%) in 1-MeTIQ levels in the SN, but TIQ levels did not change significantly in either of the studied regions.

Aging↗

PubMed1994

The effect of a vitamin E-deficient diet on amino acid levels in the substantia nigra, striatum and hippocampus of rats.

The effects of a vitamin E deficiency diet for 15 days on amino acid concentrations have been studied in the substantia nigra, striatum and hippocampus of the rat. The substantia nigra showed an increase in glutamate and GABA and a decrease of tryptophan concentration compared with controls. In the striatum, aspartate and glycine decreased, no changes were found in the amino acid concentrations in the hippocampus. The substantia nigra and striatum showed opposite results-an increase and decrease of amino acids respectively. The increase of glutamate found in substantia nigra is particularly interesting as it may suggest possible links to degenerative processes. These results suggest that vitamin E could play a crucial role in substantia nigra degeneration and that the substantia nigra could be more sensitive to an oxidative stress than other brain structures.

Amino Acids↗

PubMed1994

Phenotype variants, malignancy, and additional copies of 6p in retinoblastoma.

Thirty-four of 51 (67%) primary retinoblastomas were analyzed cytogenetically to characterize the type of events that result in additional copies of the short arm of chromosome 6 and their implications in this malignancy. Of the 34 tumors studied, additional copies of 6p were found in 14 (41%). The most frequent mechanism involved to produce additional 6p chromosomes was the isochromosome i(6p) (65%). Other mechanisms were translocations of 6p to other chromosomes (14%), tetrasomy 6 (14%), and additional derived 6q- (7%). Although i(6p) is considered a chromosome rearrangement almost exclusive to retinoblastoma, its significance remains unknown in the carcinogenesis or the progression of retinoblastoma. Our work suggests strongly that the presence or absence of additional copies of 6p defines two categories of retinoblastoma; additional 6p is associated with an undifferentiated histologic degree and invasion of the optic nerve.

Chromosomes, Human, Pair 6↗

PubMed1994

Pharmacokinetics of folinic acid and 5-methyltetrahydrofolic metabolite after repeated oral administration of calcium folinate following methotrexate treatment.

The pharmacokinetic profiles of folinic acid (FA) and its active metabolite, 5-methyltetrahydrofolic acid, were studied after oral administration of decreasing doses of calcium folinate during 37 courses of high and intermediate dose methotrexate treatment in 25 lymphoma patients. FA was administered at a dose of 6 x 50 mg in 15 courses, 6 x 25 mg in seven courses, 6 x 15 mg in 10 courses and 6 x 7.5 mg in 5 courses. FA, 5-methyltetrahydrofolic acid, methotrexate and 70H-methotrexate were assayed simultaneously by high performance liquid chromatography. When FA was administered at doses between 50 and 15 mg, maximum concentrations of both the drug and its metabolite were always obtained after 1 to 2 h and remained stable. The same was true for the equilibrium concentration of the two products at doses over 15 mg. These findings suggest saturation of absorption and metabolism of folinic acid at doses over 15 mg.

Administration, Oral↗

PubMed1994

Effect of L-arginine/nitric oxide pathway on MPP(+)-induced cell injury in the striatum of rats.

1. Protection against 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity by two nitric oxide-related compounds, N omega-nitro-L-arginine (L-NOARG) and L-arginine, was studied in the corpus striatum by means of two MPP+ perfusions separated by 24 h. Dopamine extracellular output after the second MPP+ (1, 5 and 10 mM) perfusion was considered as an index of the dopaminergic neurone damage produced by the first MPP+ (1, 5 and 10 mM) perfusion. 2. L-NOARG, systemically administered (10 mg kg-1, i.p., every 12 h for 4 days), failed to prevent the neurotoxic action of MPP+ (1 and 10 mM). On the contrary, the neurotoxic effect of MPP+ was increased by L-NOARG administration. 3. L-Arginine (10 mM) perfused 2 h before MPP+ perfusion did not protect against the neurotoxic action of high MPP+ concentrations (5 and 10 mM). At the highest MPP+ concentration used (10 mM), the increase in the extracellular output of dopamine after the second MPP+ perfusion was slower in L-arginine-treated rats than in control and L-NOARG-treated rats. 4. When MPP+ (1 mM) was perfused 2 h after L-arginine (10 mM) perfusion, there was a clear protection against MPP+ neurotoxicity. In the second MPP+ (1 mM) perfusion, the increase in the extracellular output of dopamine in L-arginine-treated rats was twice as high as for the control rats. 5. The results indicate that NO may exert a protective mechanism in the presence of a low ambient redox.

1-Methyl-4-phenylpyridinium↗

PubMed1994

High dose intravitreal foscarnet in the treatment of cytomegalovirus retinitis in AIDS.

The efficacy and tolerance of high dose intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS was studied. Foscarnet in a dose of 2400 micrograms was injected directly into the vitreous of 11 patients (15 eyes). Five patients had active retinitis (eight eyes, 53.3%), and received a 3 week induction therapy of six injections as the first step. Six patients had initial inactive retinitis (seven eyes, 46.7%), and received only maintenance therapy which consisted of a weekly injection. The main indications for intravitreal therapy were: myelosuppression, kidney toxicity, catheter related sepsis, or refusal of intravenous therapy. The patients were followed for a mean period of 16 weeks (range 8-28 weeks) and received a total of 304 injections. Vitreous foscarnet levels were measured by high performance liquid chromatography. After a 3 week course of induction therapy, complete resolution of the active retinitis was seen in 62.5% (5/8 cases), while 37.5% (3/8 cases) had partial resolution. No cases failed to respond or progress. The rate of relapse on maintenance therapy was 33% (five of 15 eyes) by 20 weeks, and two of these eyes did not respond to reinduction and progressed in involvement of the macula or optic nerve. Neither important local complications nor intraocular drug toxicity were observed. Vitreous foscarnet levels in two different patients were 896 mumol/l and 74.9 mumol/l at 22 3/4 hours and 42 1/2 hours after the injection. Intravitreal foscarnet appears to be a safe, effective, and useful alternative in patients with intolerance to intravenous and viral therapy.

AIDS-Related Opportunistic Infections↗

PubMed1993

Age-related changes on monoamine turnover in hippocampus of rats.

After pargyline treatment the turnover rates of dopamine (DA), noradrenaline (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-hydroxytryptamine (5-HT) and 5-hydroxy-3-indolacetic acid (5-HIAA) has been measured in control and aged hippocampus of the rats. In addition, the tyrosine hydroxylase (TH) activity and monoamine oxidase-A and monoamine oxidase-B activities have also been studied. The TH activity did not change in aged hippocampus as compared to controls. The monoamine oxidase-B: monoamine oxidase-A ratio increased in 26-month-old rats compared with controls. The turnover of DA, DOPAC and NA did not show significant changes while 5-HT synthesis, 5-HT accumulation rate and 5-HIAA turnover increased in aged rats. Serotonin fibers showed morphological dissimilarities between the hippocampus of young and aged rats using immunocytochemistry techniques. In aged rats aberrant serotoninergic fibers mainly appear in the molecular layer of the dentate gyrus and molecular of the hippocampal CA1. It is suggested that the aberrant morphology of 5-HT fibers may reflect the local degeneration of serotoninergic hippocampal afferents during aging. Increase of 5-HT turnover in aged might be a signal of degeneration.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Effect of ageing on monoamine turnover in the prefrontal cortex of rats.

Turnover of dopamine (DA), serotonin (5-hydroxytryptamine) (5-HT), noradrenaline (NA) and their metabolites has been measured in control and aged rats. In addition, tyrosine hydroxylase (TH) activity has been studied. After pargyline treatment, the turnover rates of DA, NA, 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), 5-HT and 5-hydroxy-3-indolacetic acid (5-HIAA) and TH activity increased in aged rats with respect to controls. At the same time the DA and 3-MT turnover increase are consistent with the hypothesis that enhanced release of DA may participate in some degenerative processes in ageing. After probenecid treatment, the turnover of homovanillic acid (HVA) was lower in aged rats than in controls. However, DOPAC turnover was higher in the aged rats. The DOPAC increase seems to indicate a reinforcement of this pathway in aged rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Regulation of the prefrontal cortical dopamine release by GABAA and GABAB receptor agonists and antagonists.

The gamma-aminobutyric acid-dopamine (GABA-DA) relationship was studied by intracerebral microdialysis in the prefrontal cortex. Nomifensine (5 microM) was included in the Ringer solution during all the dialysis experiments. Muscimol, a GABAA receptor agonist (50 and 500 microM) did not affect the extracellular output of DA and 3,4-dihydroxyphenylacetic acid (DOPAC). Baclofen, a GABAB receptor agonist (50 microM) significantly decreased the extracellular output of DA and DOPAC. On the other hand, picrotoxin and phaclofen, GABAA and GABAB receptor antagonists respectively, at a concentration of 50 microM, both significantly increased the release of DA. While the DOPAC level was affected only by picrotoxin perfusion. The present study indicates that GABA could control the release of DA in the prefrontal cortex.

3,4-Dihydroxyphenylacetic Acid↗